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Acetylcholine Promotes Ca2+and NO-Oscillations in Adipocytes Implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ Positive Feedback Loop - Modulatory Effects of Norepinephrine and Atrial Natriuretic Peptide  [PDF]
Egor A. Turovsky, Mariya V. Turovskaya, Ludmila P. Dolgacheva, Valery P. Zinchenko, Vladimir V. Dynnik
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063483
Abstract: Purpose This study investigated possible mechanisms of autoregulation of Ca2+ signalling pathways in adipocytes responsible for Ca2+ and NO oscillations and switching phenomena promoted by acetylcholine (ACh), norepinephrine (NE) and atrial natriuretic peptide (ANP). Methods Fluorescent microscopy was used to detect changes in Ca2+ and NO in cultures of rodent white adipocytes. Agonists and inhibitors were applied to characterize the involvement of various enzymes and Ca2+-channels in Ca2+ signalling pathways. Results ACh activating M3-muscarinic receptors and Gβγ protein dependent phosphatidylinositol 3 kinase induces Ca2+ and NO oscillations in adipocytes. At low concentrations of ACh which are insufficient to induce oscillations, NE or α1, α2-adrenergic agonists act by amplifying the effect of ACh to promote Ca2+ oscillations or switching phenomena. SNAP, 8-Br-cAMP, NAD and ANP may also produce similar set of dynamic regimes. These regimes arise from activation of the ryanodine receptor (RyR) with the implication of a long positive feedback loop (PFL): Ca2+→ NO→cGMP→cADPR→Ca2+, which determines periodic or steady operation of a short PFL based on Ca2+-induced Ca2+ release via RyR by generating cADPR, a coagonist of Ca2+ at the RyR. Interplay between these two loops may be responsible for the observed effects. Several other PFLs, based on activation of endothelial nitric oxide synthase or of protein kinase B by Ca2+-dependent kinases, may reinforce functioning of main PFL and enhance reliability. All observed regimes are independent of operation of the phospholipase C/Ca2+-signalling axis, which may be switched off due to negative feedback arising from phosphorylation of the inositol-3-phosphate receptor by protein kinase G. Conclusions This study presents a kinetic model of Ca2+-signalling system operating in adipocytes and integrating signals from various agonists, which describes it as multivariable multi feedback network with a family of nested positive feedback.
Atrial Natriuretic Peptide Regulates Ca2+ Channel in Early Developmental Cardiomyocytes  [PDF]
Lin Miao,Min Wang,Wen-Xuan Yin,Qi Yuan,Ying-Xiao Chen,Bernd Fleischmann,Jürgen Hescheler,Guangju Ji
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008847
Abstract: Cardiomyocytes derived from murine embryonic stem (ES) cells possess various membrane currents and signaling cascades link to that of embryonic hearts. The role of atrial natriuretic peptide (ANP) in regulation of membrane potentials and Ca2+ currents has not been investigated in developmental cardiomyocytes.
Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes phosphoinositide hydrolysis, Ca2+ release, and activation of protein kinase C  [PDF]
Kailash N. Pandey
Frontiers in Molecular Neuroscience , 2014, DOI: 10.3389/fnmol.2014.00075
Abstract: Thus far, three related natriuretic peptides (NPs) and three distinct sub-types of cognate NP receptors have been identified and characterized based on the specific ligand binding affinities, guanylyl cyclase activity, and generation of intracellular cGMP. Atrial and brain natriuretic peptides (ANP and BNP) specifically bind and activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), and C-type natriuretic peptide (CNP) shows specificity to activate guanylyl cyclase/natriuretic peptide receptor-B (GC-B/NPRB). All three NPs bind to natriuretic peptide receptor-C (NPRC), which is also known as clearance or silent receptor. The NPRA is considered the principal biologically active receptor of NP family; however, the molecular signaling mechanisms of NP receptors are not well understood. The activation of NPRA and NPRB produces the intracellular second messenger cGMP, which serves as the major signaling molecule of all three NPs. The activation of NPRB in response to CNP also produces the intracellular cGMP; however, at lower magnitude than that of NPRA, which is activated by ANP and BNP. In addition to enhanced accumulation of intracellular cGMP in response to all three NPs, the levels of cAMP, Ca2+ and inositol triphosphate (IP3) have also been reported to be altered in different cells and tissue types. Interestingly, ANP has been found to lower the concentrations of cAMP, Ca2+, and IP3; however, NPRC has been proposed to increase the levels of these metabolic signaling molecules. The mechanistic studies of decreased and/or increased levels of cAMP, Ca2+, and IP3 in response to NPs and their receptors have not yet been clearly established. This review focuses on the signaling mechanisms of ANP/NPRA and their biological effects involving an increased level of intracellular accumulation of cGMP and a decreased level of cAMP, Ca2+, and IP3 in different cells and tissue systems.
AC-NP: A Novel Chimeric Peptide with Natriuretic and Vasorelaxing Actions  [PDF]
Bao-Ying Chen,Jian-Kang Chen,Miao-Zhang Zhu,Dong-Liang Zhang,Jie-Shen Sun,Jian-Ming Pei,Hua-Song Feng,Xiao-Xing Zhu,Jian Jin,Jun Yu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020477
Abstract: The aim of this study was to evaluate the cardiovascular and renal activities of a newly designed natriuretic peptide (NP). Here, we engineered a novel 28-amino acid chimeric peptide, termed AC-NP that combined the 17-amino acid ring of C type natriuretic peptide (CNP) with the 6-amino acid N-terminus and 5-amino acid C-terminus of atrial natriuretic peptide (ANP). Both in vitro and in vivo experiments were performed to determine the actions of AC-NP. In normal rats, AC-NP proved to be more potentially diuretic, natriuretic and hypotensive compared with other NPs, such as ANP, CNP and vasonatrin peptide (VNP), which is another man-made NP. In relaxation of isolated abdominal aorta from rat, AC-NP was equally effective to ANP, CNP and VNP. Elevated levels of 3′,5′-guanosine monophosphate (cGMP) in plasma and urine cGMP excretion indicated the participation of cGMP in the functions of AC-NP. Taken together, innovative designed AD-NP might be a new candidate therapeutic peptide against cardiorenal disorders.
Effect of Professional Exercises on Brain Natriuretic Peptide
MA Babaee Beigi,A Aslani,H Sheikhani Shahin,F Daryanoosh
Iranian Cardiovascular Research Journal , 2009,
Abstract: Background: Brain natriuretic peptide (BNP) reflects myocardial wall stress. BNP activities are similar to those of atrial natriuretic peptide, including diuresis, natriuresis, hypotension and smooth muscle relaxation as well as ability to inhibit the rennin aldosterone system. It is mainly produced and released into the circulation by the ventricle in response to increased ventricular wall pressure or stretching. Therefore, BNP can be served as a marker of left ventricular dysfunction. The aim of this study was to investigate effect of various professional exercises on plasma BNP levels.Methods: We enrolled 20 consecutive healthy professional athletic males from different sporting disciplines including 5 football players, 5 volleyball players, 5 bodybuilders and 5 water- polo players. Plasma BNP samples were taken immediately before and 1 hour after exercise.Results: Plasma BNP level was significantly increased after exercise (30.01 ± 23.46 vs. 16.72 ± 10.86 pg/ml; P= 0.042). The highest increase in BNP level was found among volleyball players (mean values: 19.12 to 43.38 pg/ml; 126.3% increase after volleyball) compared to other exercises. Conclusion: Exercise can increase plasma BNP levels, particularly among volleyball players.
Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through the cGMP/cGMP-dependent protein kinase pathway  [cached]
Chun-Yu Cai, Zheng-Xu Cai, Xin-Yi Gu, Lu-Juan Shan, Yong-Xiao Wang, Xue-Zhe Yin, Qing-Hui Qi, Hui-Shu Guo
World Journal of Gastroenterology , 2008,
Abstract: AIM: To systematically investigate if cGMP/cGMP-dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle.METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique.RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastric antral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor.CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/PKA pathway.
Atrial natriuretic peptide and feeding activity patterns in rats
Brazilian Journal of Medical and Biological Research , 1997, DOI: 10.1590/S0100-879X1997000400006
Abstract: this review presents historical data about atrial natriuretic peptide (anp) from its discovery as an atrial natriuretic factor (anf) to its role as an atrial natriuretic hormone (anh). as a hormone, anp can interact with the hypothalamic-pituitary-adrenal axis (hpa-a) and is related to feeding activity patterns in the rat. food restriction proved to be an interesting model to investigate this relationship. the role of anp must be understood within a context of peripheral and central interactions involving different peptides and pathways
Atrial natriuretic peptide and feeding activity patterns in rats  [cached]
Oliveira M.H.A.,Antunes-Rodrigues J.,Gutkowska J.,Leal A.M.O.
Brazilian Journal of Medical and Biological Research , 1997,
Abstract: This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways
Brain natriuretic peptide: Diagnostic potential in dogs  [PDF]
Spasojevi?-Kosi? Ljubica
Veterinarski Glasnik , 2009, DOI: 10.2298/vetgl0906381k
Abstract: The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP) has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .
Atrial Natriuretic Peptide and Adiponectin Interactions in Man  [PDF]
Andreas L. Birkenfeld,Michael Boschmann,Stefan Engeli,Cedric Moro,Ayman M. Arafat,Friedrich C. Luft,Jens Jordan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043238
Abstract: Reduced circulating natriuretic peptide concentrations are independently associated with insulin resistance and type 2 diabetes, while increased natriuretic peptide levels appear to be protective. Observations in vitro and in heart failure patients suggest that atrial natriuretic peptide (ANP) promotes adiponectin release, an adipokine with insulin sensitizing properties. We tested the hypothesis that ANP acutely raises adiponectin levels in 12 healthy men. We infused ANP intravenously over 135 minutes while collecting venous blood and adipose tissue microdialysates at baseline and at the end of ANP-infusion. We obtained blood samples at identical time-points without ANP infusion in 7 age and BMI matched men. With infusion, venous ANP concentrations increased ~10 fold. Systemic and adipose tissue glycerol concentrations increased 70% and 80%, respectively (P<0.01). ANP infusion increased total adiponectin 14±5% and high molecular-weight (HMW)-adiponectin 13±5% (P<0.05). Adiponectin did not change in the control group (P<0.05 vs. infusion). ANP-induced changes in HMW adiponectin and adipose tissue lipolysis were directly correlated with each other, possibly suggesting a common mechanism. Our data show that ANP acutely increases systemic total and HMW-adiponectin concentrations in healthy subjects. Our study could have implications for the physiological regulation of adiponectin and for disease states associated with altered natriuretic peptide availability.
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